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Table 1 Sensitivity of cell lines to gemcitabine alone or in combination with MK-8776

From: Sensitization of human cancer cells to gemcitabine by the Chk1 inhibitor MK-8776: cell cycle perturbation and impact of administration schedule in vitro and in vivo

A. Gemcitabine and MK-8776 0–24 h
Cell line IC50(nmol/L)
  Gem alone Gem + 200 nmol/L MK-8776 Gem + 2 μmol/L MK-8776
U251 36.6 ± 8.8 15 ± 5.5 (2.4) 6.5 ± 1.5 (5.6)
HCT115 25 ± 5 13.8 ± 1.3 (1.8) 5.1 ± 1.1 (4.9)
SW620 83.3 ± 16 30 ± 0 (2.8) 4.8 ± 0.9 (17.4)
IGROV-1 25 ± 5 5.2 ± 1.1 (4.8) 3.5 ±1.5 (7.1)
HCT116 13.8 ± 1.3 5.5 ± 0.5 (2.5) 3.3 ± 0.3 (4.2)
MCF10A 13 ± 6.1 5.2 ± 2.4 (2.5) 2.8 ± 1.1 (4.6)
MiaPaCa-2 26.5 ± 4.3 4.2 ± 0.8 (6.3) 2.2 ± 1.2 (12.0)
MDA-MB-231 18.5 ± 7.1 4.4 ± 0.81 (4.2) 1.5 ± 0.44 (12.3)
HCC2998 15 ± 5 3.8 ± 1.3 (3.9) 1.5 ± 0.4 (10.0)
U87 7.5 ± 1.3 2.7 ± 0.4 (2.8) 1.5 ± 0.3 (5.0)
MDA-MB-435 8.6 ± 3.2 1.5 ± 1.5 (5.7) 0.4 ± 0 (21.5)
SNB19 10 ± 3.5 1.3 ± 0.08 (7.7) 0.15 ± 0.03 (66.7)
U20S 32.5 ± 2.5 10.5 ± 4.5 (3.1) DEAD
A498 22.5 ± 2.5 3.5 ± 1.5 (6.4) DEAD
TK10 3.4 ± 1.6 2.8 ± 1.3 (1.2) DEAD
AsPC-1 14 ± 1 3.3 ± 0.2 (4.2) DEAD
B. Gemcitabine 0–24 h; MK-8776 18–24 h
U251 36.6 ± 8.8 32.5 ± 2.5 (1.1) 12.5 ± 2.5 (2.9)
MDA-MB-231 18.5 ± 7.1 12.5 ± 5.5 (1.5) 4.6 ± 0.8 (4.0)
U87 7.5 ± 1.3 5 ± 0.6 (1.5) 2.8 ± 0.16 (2.7)
MDA-MB-435 8.6 ± 3.2 8 ± 2 (1.1) 0.77 ± .73 (11.2)
AsPC-1 14 ± 1 7.8 ± 2.2 (1.8) 1.7 ± 0.23 (8.2)
C. Gemcitabine 0–6 h; MK8776 18–24 h
U251 250 ± 51 187 ± 38 (1.3) 113 ± 18.5 (2.2)
MiaPaCa-2 175 ± 25 90 ± 35 (1.9) 39 ± 1 (4.5)
MDA-MB-231 60.5 ± 10.3 35 ± 9.6 (1.7) 19.2 ± 2.3 (3.2)
U87 12.6 ± 3.9 9 ± 2.1 (1.4) 5.3 ± 0.9 (2.4)
MDA-MB-435 41.6 ± 19.7 22.5 ± 7.5 (1.8) 5.5 ± 2.5 (7.6)
SNB19 75 ± 0 35 ± 5 (2.1) 16.5 ± 1.5 (4.5)
AsPC-1 115 ± 11.9 53.3 ± 6.7 (2.2) 12 ± 1.7 (9.6)
  1. Following treatment as indicated, drugs were removed and cells were incubated for an additional 5–7 days and the IC50 for gemcitabine determined.
  2. Values reflect mean +/− SEM with n = 2–5; parenthesis = fold sensitization.
  3. “DEAD” = MK-8776 alone markedly suppressed growth so no cumulative cytotoxicity calculable.